The research studies proposed in this application will provide new information on the microvascular angiopathy of diabetes. These studies will utilize streptozotocin diabetic rats studied at approximately 8 and 16 weeks of age. The proposal is divided into two areas: 1) reactivity of the microcirculation and 2) alterations in regulatory mechanisms during diabetes. In the reactivity studies, the responsiveness of arteriolar and venular vessels at several different anatomical levels within the cremaster muscle will be studied using in vivo television microscopy. Alterations in the reactivity of the vascular smooth muscle that occur during diabetes will be evaluated the responsiveness of vessels to topically applied norepinephrine, and comparing the dose-response curves to those obtained in normal animals. Indirect measurements suggest that vascular reactivity may be altered during diabetes, but direct measurements of these alterations in the intact microcirculation have not been presented. In the second study, the ability of the tissues to regulate their own blood flow (autoregulation) during diabetes will be investigated by altering the arterial and venous pressures perfusing the cremaster muscle, and directly measuring the changes in diameter, velocity, pressure and flow within individual arterioles at several anatomical levels. The autoregulatory responses obtained in diabetic animals will be compared with those obtained in normal animals to determine if the diabetic processes alter the regulatory potential within skeletal muscle tissue. In summary, the research studies proposed in this application will provide direct, quantitative measurements of the functional changes that occur within the microcirculation during the development of diabetes.